LUNA18 for Solid Tumors

Not currently recruiting at 20 trial locations

Overseen By Clinical trials information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Chugai Pharmaceutical

Disqualifiers: Cardiovascular disease, CNS malignancy, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LUNA18 to determine its safety and effectiveness for individuals with solid tumors that have spread or cannot be cured with standard treatments. The study examines different doses of LUNA18, both alone and in combination with another cancer drug, cetuximab, to identify the optimal dose and assess its efficacy. Suitable candidates for this trial include those with solid tumors featuring specific gene changes (RAS alterations) for whom other treatments have failed or are not viable. As a Phase 1 trial, this research aims to understand how LUNA18 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that LUNA18 is likely to be safe for humans?

Research has shown that LUNA18, a new treatment being tested for solid tumors, is under study to determine its safety for people. Since the research is in its early stages, detailed safety information is limited. However, LUNA18 is similar to other drugs called Aurora kinase inhibitors, which have generally been safe in past studies.

In this early testing phase, researchers aim to observe how patients react to LUNA18. They are monitoring for any side effects and determining safe doses. While specific side effects for LUNA18 are not yet available, similar treatments have had manageable side effects in other studies.

In parts of the study where LUNA18 is used with cetuximab, a drug already used for some cancers, past research on cetuximab alone has shown it to be relatively safe, though it can cause side effects like skin problems or low magnesium levels.

This phase of the trial focuses on safety, so participants will be closely monitored to catch any issues early. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which typically involve chemotherapy, radiation, or surgery, LUNA18 is unique because it is an oral capsule designed to be used at different dosages and in combination with cetuximab, a monoclonal antibody. This approach allows for more personalized dosage adjustments and potentially enhances the treatment's efficacy by targeting specific tumor pathways. Researchers are excited about LUNA18 because it represents a novel administration method that could improve patient convenience and treatment outcomes by optimizing drug delivery and effectiveness.

What evidence suggests that LUNA18 could be an effective treatment for solid tumors?

Research has shown that LUNA18 effectively reduces tumor growth and spread in animal studies. It targets specific proteins involved in cancer cell communication and resistance. In this trial, some participants will receive LUNA18 alone, while others will receive it in combination with cetuximab, another cancer drug. Researchers aim to determine how this combination may improve treatment responses. Although human studies offer limited information, these findings provide a hopeful basis for LUNA18's potential in treating solid tumors. ^{1 2 6 7 8}

Who Is on the Research Team?

Sponsor Chugai Pharmaceutical Co. Ltd

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors not responding to standard treatments can join. They must be relatively healthy (ECOG status of 0 or 1) and have RAS mutation-positive tumors that are measurable. Those with serious heart conditions, uncontrolled diseases, lung complications like ILD, brain cancer, or active brain metastases needing treatment cannot participate.

Inclusion Criteria

My cancer is advanced, cannot be cured with surgery, and standard treatments haven't worked or I can't tolerate them.

I am fully active or can carry out light work.

Patients with measurable disease per RECIST v1.1

Exclusion Criteria

I do not have any severe, uncontrolled illnesses like heart, lung, or kidney diseases.

I do not have serious heart problems like recent heart attacks or unstable heart rhythms.

I have a brain tumor or cancer spread to my brain that needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients receive LUNA18 capsule(s) at escalated doses to determine safety and tolerability

6-9 days for Cycle 0, 28 days for Cycle 1

Cohort Expansion

Patients receive LUNA18 capsule(s) at the recommended dose, alone or in combination with cetuximab

Up to approximately 43 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LUNA18

Trial Overview The study is testing LUNA18's safety and effectiveness alone or with other cancer drugs in patients with advanced solid tumors. It's a Phase 1 trial where doses increase gradually to find the right balance between safety and potential benefits.

How Is the Trial Designed?

Group I: Dose finding part (Part D) Experimental Treatment 2 Interventions

Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses

Group II: Dose escalation part (Part A) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at escalated doses

Group III: Cohort expansion part (Part E) Experimental Treatment 2 Interventions

Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose

Group IV: Cohort expansion part (Part C) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at the recommended dose

Group V: Biomarker part (Part B) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A

Group VI: Backfill part (Part AA) Experimental Treatment 1 Intervention

Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A

Who Is Running the Clinical Trial?

Chugai Pharmaceutical

Lead Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Published Research Related to This Trial

K18, a new antitumor agent combining human immunoglobulin with melphalan, showed promising antitumor effects in two animal models of metastasis, specifically in mice with Lewis lung carcinoma and colon-26 tumors.

Oral administration of K18 significantly reduced the number of lung nodules in mice with tumors transplanted via the tail vein, indicating its potential efficacy in treating metastatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effect of K18 on metastatic models. Fujii, T., Furusho, T., Niimura, K., et al.[2013]

In a phase II trial involving 16 patients with advanced solid tumors, vorinostat was found to be tolerable only at a dose of 200 mg twice daily, as higher doses led to significant dose-limiting toxicities such as anorexia and thrombocytopenia.

Despite some disease stabilization in eight patients, there were no confirmed responses to vorinostat, indicating that while it may be safe at lower doses, its efficacy in this patient population remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. Vansteenkiste, J., Van Cutsem, E., Dumez, H., et al.[2021]

Between 2017 and 2021, the FDA approved 161 new therapeutic agents for solid tumors, marking a significant increase in treatment options for cancer patients.

However, only 27% of these approvals demonstrated clear evidence of improving overall survival, with many relying on surrogate endpoints, indicating a need for better quality and assurance of clinical benefits in new cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An appraisal of FDA approvals for adult solid tumours in 2017-2021: has the eagle landed? Cherny, NI.[2022]

In a review of 14 trials involving 12,567 patients with advanced non-small-cell lung cancer (NSCLC), a strong association was found between overall response rate (ORR) and progression-free survival (PFS), indicating that treatments that improve ORR likely also enhance PFS.

However, no significant association was observed between ORR and overall survival (OS), suggesting that while responders have better PFS and OS, factors like treatment cross-over and prolonged survival after disease progression may complicate the relationship between these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. Blumenthal, GM., Karuri, SW., Zhang, H., et al.[2022]

In a study of 12,081 women with stage I-IIIa, node-negative, hormone receptor-positive breast cancer, Oncotype DX recurrence scores were found to be similarly received by both non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients, indicating equitable access to testing.

Despite comparable testing, NHB women with low recurrence scores had a significantly higher risk of breast cancer mortality compared to NHW women, suggesting that factors beyond the Oncotype DX scores may contribute to racial disparities in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncotype DX recurrence score implications for disparities in chemotherapy and breast cancer mortality in Georgia. Collin, LJ., Yan, M., Jiang, R., et al.[2023]

A study comparing real-world outcomes of 107 women with metastatic breast cancer receiving letrozole to 222 women in the PALOMA-2 trial found similar median progression-free survival rates (18.4 months vs. 16.6 months), suggesting that real-world data can effectively reflect clinical trial results.

Response rates were also comparable between the two groups (41.8% in the real-world cohort vs. 39.4% in PALOMA-2), indicating that electronic health record data can provide reliable insights into treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer. Huang Bartlett, C., Mardekian, J., Cotter, MJ., et al.[2020]

In a phase 2 trial involving 125 patients with recurrent/metastatic head and neck squamous-cell carcinoma, the combination of palbociclib and cetuximab did not significantly improve overall survival compared to placebo and cetuximab, with median overall survival times of 9.7 months and 7.8 months respectively.

The most common side effects associated with palbociclib were rash and neutropenia, indicating that while the treatment was generally tolerated, it did come with notable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial. Adkins, DR., Lin, JC., Sacco, A., et al.[2021]

The phase I study of MLN8237 (alisertib) in 87 adult patients with advanced solid tumors demonstrated that the drug is generally well-tolerated, with common side effects including fatigue, nausea, and neutropenia.

At the maximum tolerated dose of 50 mg twice daily, MLN8237 effectively inhibited Aurora A kinase activity, leading to a partial response in 1% of patients and stable disease in 23% for at least 3 months, suggesting potential efficacy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Dees, EC., Cohen, RB., von Mehren, M., et al.[2021]

The maximum-tolerated dose (MTD) of MK-0457, a novel pan-Aurora kinase inhibitor, was determined to be 64 mg/m²/h, with dose-limiting toxicities including severe neutropenia and herpes zoster observed at higher doses.

MK-0457 was generally well tolerated, with nearly half of the 27 patients experiencing stable disease, suggesting potential efficacy, particularly in combination with other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Traynor, AM., Hewitt, M., Liu, G., et al.[2022]

Aurora kinase inhibitors, targeting Aurora A and B, have shown promising anti-tumor activity in clinical trials, particularly in advanced cancers like ovarian cancer and acute myelogenous leukemia.

While these inhibitors can lead to significant responses, including complete remissions, they are also associated with notable side effects such as febrile neutropenia, gastrointestinal toxicity, and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress. Falchook, GS., Bastida, CC., Kurzrock, R.[2022]

K18, a new antitumor agent, demonstrated low acute toxicity in animal studies, indicated by high LD50 values, suggesting it is safe for further testing.

K18 effectively inhibited tumor growth in both an experimental animal model (Walker 256) and a human tumor model (RCC-13) in nude mice, and it showed a unique ability to accumulate and persist at the tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects of 3-[p-(N,N-bis-(2'-chloroethyl)amino)-phenyl]-L- alanine conjugated with human immunoglobulin (K18). Yoshimura, M., Niimura, K., Fujii, M., et al.[2013]

In a study of 250 clear cell renal cell carcinoma (ccRCC) cases, higher levels of the transcription factor SOX18 were linked to more advanced cancer stages and poorer patient survival, suggesting its role in promoting cancer progression.

SOX18 not only enhances ccRCC carcinogenesis and metastasis but also helps cancer cells resist the effects of the drug cabozantinib, indicating that targeting SOX18 could be a potential strategy for improving ccRCC treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcription Factor SOX18 Promotes Clear Cell Renal Cell Carcinoma Progression and Alleviates Cabozantinib-Mediated Inhibitory Effects. Huaqi, Y., Caipeng, Q., Qiang, W., et al.[2020]

SOX18 and IL-6 levels are elevated in osteosarcoma compared to normal bone tissues, indicating their potential roles in the disease's progression.

IL-6 appears to regulate SOX18 expression, promoting osteosarcoma cell proliferation and inhibiting apoptosis, suggesting that targeting this pathway could be a therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-6 upregulates SOX18 expression in osteosarcoma. Wu, Z., Yang, W., Liu, J., et al.[2022]

In a first-in-human trial involving 61 patients with advanced solid tumors, the maximum tolerated dose (MTD) of the Aurora A kinase inhibitor MLN8054 was determined to be 60 mg taken four times daily for 14 days, with reversible somnolence identified as the dose-limiting toxicity.

The study found that MLN8054 was rapidly absorbed and had a dose-proportional exposure, but the side effects limited the ability to reach plasma concentrations needed for effective target modulation, indicating the need for further investigation with a second-generation inhibitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors. Dees, EC., Infante, JR., Cohen, RB., et al.[2021]

SOX18 is overexpressed in osteosarcoma (OS) patients and cell lines, and its silencing leads to significant cell cycle arrest and apoptosis, as well as reduced migration and invasion of OS cells, indicating its role in promoting tumor malignancy.

The study suggests that targeting SOX18 could be a promising therapeutic strategy for osteosarcoma, as it regulates key proteins involved in cell growth and survival, such as p53 and Bcl-2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneous expression and biological function of SOX18 in osteosaroma. Zhu, D., Yang, D., Li, X., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05012618

NCT05012618 | A Dose-escalation Study of LUNA18 in ... This is a Phase 1 dose-escalation and cohort expansion study that will evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-8-2021-c24af

LUNA18 for Solid Tumors · Info for Participants Yes, LUNA18 is a promising treatment for solid tumors. It has shown strong anti-tumor effects in animal studies, including reducing tumor growth and spreading.

3. synapse.patsnap.com synapse.patsnap.com/blog/roche-clinical-trial-phase-i-of-oral-cyclic-peptide-kras-g12d-inhibitor

Roche Clinical Trial Phase I of Oral Cyclic Peptide KRAS ... Following oral administration, the bioavailability of compound luna18 in these four animals ranged from 21-47%. These results suggested that ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S221138352400056X

REVIEW Targeting RAF dimers in RAS mutant tumors This review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treatment in tumors with RAS mutations.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12295999/

Innovative Peptide Therapeutics in the Pipeline: Transforming ... While surgical resection is effective for localised solid tumours, incomplete removal may necessitate repeated procedures, potentially ...

6. medchemexpress.com medchemexpress.com/luna18.html?srsltid=AfmBOorFMjFanTkdnvJ1AMjafQtfxkzTaLSBgR-CMJqZcUHrfBk8vAug

LUNA18 (Paluratide) | KRAS Inhibitor, ERK ... LUNA18 is an orally-available cyclic peptide KRAS and ERK inhibitor. LUNA18 phosphorylates ERK and AKT and decreases cell proliferation in RAS-mutated ...

7. uat-cr.dapstudies.com uat-cr.dapstudies.com/en/find-trials/Study/NCT05012618

NCT05012618 - Clinical Research A Dose-escalation Study of LUNA18 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion). · Interested?

8. ctv.veeva.com ctv.veeva.com/study/a-dose-escalation-study-of-luna18-in-patients-with-locally-advanced-or-metastatic-solid-tumors-with

A Dose-escalation Study of LUNA18 in Patients With Locally ... This is a Phase 1 dose-escalation and cohort expansion study that will evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary ...